Optic Neuropathies

Diagnosis and Management

Consider

God’s Wonders

Job 37:14

Shiprock,New Mexico

Optic Neuropathies are Difficult Diagnoses

Even experts in Neuro-ophthalmology have trouble finding the causes of many cases.

The case descriptions herein were developed for educational purposes and are for the most part composites , not necessarily of any particular patients.

The Disc Optic Neuropathies

1. No Change – appears normal

2. Cupping – Glaucoma

3. Pallor – Atrophy

4. Elevation – Possible Edema

5. Unusual– e.g. drusen, dysplastictumor, etc.

Suggests Chronic process or

past insult

Usually not pallor of

the remaining NR rim

Elevation suggest Edema or

Congenital Anomaly - clues for

edema will be given

Symptoms and Signs of an Optic Neuropathy

1. Sudden or Gradual Loss of Vision or Visual Field, or Color Vision.

2. RAPD – Relative Afferent Pupil Defect

3. Disc Changes – Edema, Pallor, Hemorrhages

4. Unexplained Visual Loss – “normal eye exam”

Basic Differential DiagnosisCINTAVO* (mnemonic) C - Congenital / Familial / Genetic

I - Inflammatory: Infectious / Allergic / Autoimmune

N - Neoplastic

T - Traumatic / Toxic

A - Aging: Degenerative

V - Vascular: Ischemia / Malformation / Hemorrhage

O - Other (OMNI-P): Obstruction / Compression

Medication

Nutritional / Metabolic

Iatrogenic

Pressure related: Blood, ICP, IOP

*Cintavo is a real word: Italian first-person singular, imperfect indicative of cintare - “to enclose or wrap up”

Optic Neuropathy?Differential Diagnosis

1. Congenital Defect in Optic Nerve

2. Hereditary – e.g. Leber’s Hereditary ON

3. High Intracranial Pressure

4. Inflammatory – Optic Neuritis

5. Neoplastic – Optic Nerve Tumor or Infiltration

6. Traumatic Neuropathy

7. Vascular – Ischemic Optic Neuropathy (ION)

8. Toxins / Medications

9. Compression – Tumor, TED, aneurysm

10. Nutritional Deficiency – e.g. B12, folate

11. Elevated Intraocular Pressure

Disc Edema

High ICP

Ischemia – ION

Inflammation – Classic Optic Neuritis – or Atypical Optic Neuritis

Infiltrative – e.g. Leukemia, Lymphoma, Sarcoidosis

Hereditary – e.g. LHON

Compression – tumor, large muscles(Graves) or vessel (e.g. carotid a.)

Toxic - e.g. Methanol, Ethylene Glycol, Ethambutol

Ocular- disc edema is false localizing sign, e.g.

Venous stasis (BRVO CRVO), hypotony, posterior scleritis, uveitis (including: AMPPE, MEWDS)

ORMAYBE NOT EDEMA, BUT SOMETHING THAT LOOKS LIKE IT

e.g. Anomalous Congenital Disc Elevation

or Abnormal Disc Vessels or growths

Approach to Patient with

Suspected Optic Neuropathy

1. Logical Analysis - Do Complete 8 Point Eye Exam

2. Think about the more common things First:1. Papilledema2. AION3. Optic Neuritis (Classic)

3. If the history / exam or the clinical course does not fit one of these problems then you must consider further problems and evaluation.

Big 3

1. Papilledema

Optic Nerve Head Swelling Secondary to

Increased Intracranial Pressure

SymptomsHeadacheTransient Visual LossPulsatile Tinnitus

Concern for Intracranial Problem

Colloidal Cyst

obstructive

hydrocephalus

Typical PapilledemaPresentation

• Symptoms:

Headache – Chronic, Nausea/Vomitting

Tinnitus

Transient Visual Obscurations (seconds)

• Good vision early on:VA good

VF: Usually normal or just

enlarged Blind Spots

• Usually Bilateral Disc Edema*www.neuroophthalmology.ca/.../case1

Chronic Papilledema

• Early Papilledema – no or little Visual Loss

• But, with continued High ICP Chronic Papilledema

Disc atrophy and Visual deterioration

• Visual Loss can sometimes be

reversed if the ICP can be lowered

Treatment:

Treat underlying condition if possible

but if vision is deteriorating then

Consider Medical and Surgical Treatments

Acute Visual Loss in Papilledema

• With Visual Loss….

• Treat underlying condition if possible,

• BUT IF VISION IS GETTING WORSE THEN CONSIDER

• Medical: Acetazolamide 500 mg PO 2x/d or 250 mg IV 4x/d

• Methyprednisolone IV 250 mg 4x/d or1.0 gram each day for 3 days

• Surgical: Lumbar Puncture (Drain)

• Optic Nerve Sheath Decompression

• or Shunting (LP or VP) Procedures

Optic Atrophy after Prolonged Severe Papilledema and Hypertension

Right Left

Increased Intracranial PressureDifferential Diagnosis

1. Hypertension – severe elevation

2. Intracranial Tumor, AVM, Carcinomatous Meningitis

3. Medications -Vitamin A, Accutane, Tetracyclines, Birth Control (BC) pills, Corticosteroid withdrawal, Growth Hormone Supplement, Thyroid supplementation, Lithium

4. Toxic: Ethylene Glycol, Lead (Pb)

5. Infection: Meningitis, Encephalitis; Lyme, HIV, post - Varicella, Malaria, Abscess

6. CNS Inflammation, Vasculitis, e.g. Lupus

7. Trauma, Hematomas, Sub- Arachnoid hemorrhage

8. Obstruction to Venous Drainage –Venous Sinus Thrombosis – hyper-coagulable states, middle ear or mastoid infections

9. Hydrocephalus, Chiari Malformation, Craniosynostosis

10. Endocrine: Addisons, Hypoparathyroidism, Weight Gain

11. Other: Sleep Apnea, Anemia, Thyroid dysfunction

12. Idiopathic Intracranial Hypertension (IIH)– Pseudotumor Cerebri – Rule Out Diagnosis

Evaluation of Increased Intracranial Pressure

1. Further History and Vital Signs- Medications, Medical/Surgical Problems, High BP

2. CT or MRI of BrainMight also consider MRV (MR Venography) for venous thrombosis

3. IF CT/ MRI is negative for Tumors or Malformations/obstructions:can consider Lumbar Puncture (LP)

FOR: Opening Pressure and CSF Analysis (For RBC, WBC, Tumor cells, Glucose, Protein, Antibodies, Cytology)

4. If testing (Imaging and Lab for Blood and CSF are negative)

then consider diagnosis of IIH / Pseudotumor Cerebri

2. AION (Anterior Ischemic Optic Neuropathy)

Ischemic Infarction of Optic Nerve Head

Signs and Symptoms:

Sudden Unilateral Visual LossVA and or VF

Usually Painless

VF loss – often respects horizontal midline,

frequently Altitudinal – most common Inferior Altitudinal

+ RAPD

Disc Edema

ION - Ischemic Optic Neuropathy

PION - posterior (no disc edema)

Need to differentiate from Retrobulbar optic neuritis

AION – anterior (disc edema)

• AAION - associated with Giant Cell Arteritis (GCA)

• NAION (also NAAION)– associated with other systemic conditions.

Need to differentiate from optic neuritis/ papillitis

Risk Factors for AION*

• Older Age

AION most common optic neuropathy in pts > 50yo**

• Vasculitis - Giant Cell Arteritis (GCA) AAION (Arteritic AION)

NAION• Diabetes Mellitus, Hypertension, Hyperlipidemia

• Smoking

• “Disc at Risk” – small C/D – crowded disc

• Sleep Apnea

• Nocturnal Hypotension

• Acute Hypotension – after - trauma, surgery

• Post Cataract Extraction

• Medications: Interferon, Amiodarone, Viagra?

NAION Non-Arteritic Anterior Ischemic Optic Neuropathy

• Often Sectoral Edema, should resolve in 6-8 weeks (If not resolve consider something else)

• Development of Sectoral pallor later on (2-3 mo).

• Visual Recovery is usually poor to modest• 15% Fellow Eye involvement in 5 years – work to decrease that risk

• Neuroimaging not needed in classic case of NAION

• Treatment: Corticosteroids - Not Proven Useful - except for cases of GCA (AAION)ASA qd – prevention of involvement other eye?Transvitreal Optic Disc Decompression, Intravitreal Avastin,

Higher Dose Prednisone ?? No effective treatments shown

• Referral to PCP or Cardiologist important to address medications, vascular risk factors and possible also arrange for a sleep study for Obstructive Sleep Apnea

AAION – Arteritic AION

• Mean Age 70 yo ; 5-10% of patients with AION

• Classic Symptoms: Head/ Temporal Pain, Scalp Tenderness,Jaw Claudication, Anorexia, Malaise, Joint Pain, Symptoms of PMR

• Severe Visual Loss <20/200• Chalky White Disc Edema• AION is most common ocular manifestation of GCA,

but other possibilities include: CRAO, Choroidal infarction, CN Palsy, etc.

• Diagnosis: Clinical Signs and Symptoms, Elevation of ESR and CRP, Temporal Artery Biopsy

• Treatment: Systemic Steroids: IV or POTaper (1-2 months) and Long Term Treatment (2 years or more)

• Risk of Fellow Eye Involvement: 80-95% if untreated

Definitions

1. Typical Optic Neuritis – A Clinical Diagnosis with a classic presentation of painful sudden loss of vision in one eye suggestive of a demyelinating optic neuritis that will usually show a good visual recovery over weeks.

2. Atypical Optic Neuritis – Non-Classic presentation of optic neuritis with involvement of one or both eyes with poor visual recovery or progression of visual loss.

3. Papillitis – Optic Neuritis associated with visible edema of the optic disc on fundus exam

4. Anterior Ischemic Optic Neuropathy (AION)– Interruption of blood flow to the optic nerve resulting in sudden painless loss of vision in one eye and disc edema

3. Classic Optic Neuritis

• Unilateral sudden loss of vision

Women > Men

• Eye Pain, Pain on eye movement

• Age 20-50 years old (Younger)

• Usually marked decrease in visual acuity < 20/200

• + RAPD

• Disc swelling often absent (Retrobulbar)

Classic Optic Neuritis• Visual Field loss:

central scotoma, altitudinal, arcuate, etc

• Color Vision Deficits

• Usually good visual recovery after 3-4 weeks- e.g. 20/20

• Usually no or little optic nerve pallor develops

• Steroids of ultimately little help

– might affect rate of recovery visual recovery is unaffected

ONTT – Optic Neuritis Treatment Trial

Neuroimaging? Yes, but not to make diagnosis of optic neuritis - but to look for white matter lesions suggestive of demyelination disease – like MS.

Possible Other Causes of Optic Nerve Inflammation

Demyelinating: Neuromyelitis Optica = NMO

Autoimmune Optic Neuropathy

Systemic Autoimmune Disorders: Lupus, Bechets, Sjogrens syndrome

Viral, Post-Viral, Post-immunization

Other infectious: Herpes: HSV, VZV, CMV, Syphilis, Toxoplasmosis, Cryptococcus, Hepatitis A, B, and C, Bartonella / Cat Scratch*, Lyme, TB, Measles, Primary HIV, Typhus

Contiguous Inflammation : Encephalitis, Meningitis (high ICP and inflammation)Orbit (orbital pseudotumor – e.g. optic perineuritis)Sinuses -Infectious (including fungal), Inflammation (Wegener’s Granulomatosis)

Sarcoidosis

CNS Vasculitis? – Primary or Secondary: Autoimmune Disease (e.g. Wegener’s, SLE, GCA, etc.)Toxic (Amphetamine, Cocaine) , Neoplastic, Infectious

Post-Partum

Chronic relapsing Inflammatory Optic Neuropathy (CRION)

Retrobulbar Papillitis

Usually will have more atypical

presentation and course

Demyelinating Optic Neuritis

1. Typical Demyelinating Optic Neuritis Idiopathic or associated with Multiple Sclerosis

2. Neuromyelitis Optica - Spectrum Disorder: NMO-SDcan be associated with other autoimmune disorders like SLE

1. + Aquaporin - 4 antibody form

2. negative AQP-4 form has more stringent clinical criteria –including 2 core clinical characteristics – including one from:

a) optic neuritis, transverse myelitis or area postrema* syndrome

3. Myelin Oligodendrocyte Glycoprotein Antibody (MOG- IgG) - associated optic neuritis.

* The area postrema is a chemoreceptor zone involved in the central control

of emesis. It is located at the floor of the fourth ventricle, in the dorsal

medulla. The area postrema syndrome is defined as episode of otherwise

unexplained hiccups or nausea and vomiting due to a lesion in this sensitive

chemoreceptor region.

Factor NAION Optic Neuritis Papilledema

Age

Eye Pain

Acute Visual Loss

RAPD?

Disc Edema

VF defects

C/D

Visual Recovery

Imaging Needed?

Factor NAION Classic Optic Neuritis Papilledema

Age Older > 50 Younger <50 Any Age

Eye Pain <10% 70-90% No Eye Pain, but Headache

Acute Visual Loss Yes Yes Usually Not

RAPD? Yes Yes No

Disc Edema 100%

Unilateral

~ 25%

Unilateral

Usually Bilateral

VF defects Usually

Altitudinalbut others possible

Many PossibleCentral, altitudinal, arcuate, etc

Early- Enlarged BS

Chronic - arcuate, constriction, etc

C/D Small (disc at risk) No association No association

Visual Recovery Poor - Modest 33% of patients 2-3 lines

Usually good Good if cause treated early

Imaging Needed? NO YES - MRI YES* - CT or MRI

What if patient’s presentation or clinical course is not like any of the natural histories?

• Obtain Further History or Physical Findings thinking about diagnostic alternatives. Do automated VF testing if not already done.

• Consider Testing based on your history and exam

- Erythrocyte Sedimentation Rate (ESR, VS)

- Neuro-Imaging – CT or MRI

- Further Blood and Imaging Studies

- Lumbar Puncture (Opening pressure, CSF analysis)

Further Testing Options To Consider in Optic Neuropathies

• CBC, C-Reactive Protein

• ANA, ANCA

• FTAbS, RPR, Bartonella Henselae Titres, Lyme Titres, HIV

• B12, Thiamine, Folate

• Testing for Sarcoidosis: ACE (Angiotensin converting enzyme level),

Chest X-Ray, Gallium Scan

• Heavy metals Screening (As,Hg,Pb, Thallium) – urine or blood

• Tuberculous Testing: PPD, Quantiferon

• Blood for Leber’s Mitochondrial DNA Mutation

• Further antibody testing for Vasculitis

• Lumbar Puncture for OPENING PRESSURE and CSF ANALYSIS

(CBC, Protein*, Glucose, Gram Stain and Cultures, Antibodies (RPR, Oligoclonal bands, etc.)

Lumbar PunctureOpening Pressure

in mm (or cm) H2O

NormalsStandard Guideline: < 200 (<20)AAFP: 10-100 (<8 yo) 60-200 (> 8 yo) <250 (obese)

N Engl J Med – 2010; 363:891Reference range for cerebrospinal fluid opening pressure in

children11.5-28.0 cm H2O

Conclusions:

1) > 250 mm H2O – definitely elevated?Opening pressures can be falsely elevatedMust take opening pressure in clinical contextIs there obvious disc edema?

Opening Pressure in Classic Lateral Decubitus Position,

However …

Lumbar Puncture

CSF Analysis

1. Cell Counts Normal < 5 WBC per mm3

WBC - elevated in infection ( Pyogenic / Bacterial WBC >1000 - mainly PMNs)

“aseptic meningitis” Viral – (WBC <100 lymphocytosis), Atypical Bacterial (e.g. Mycobacterial), Fungal (e.g. Cryptococcus), Parasitic (e.g. Toxoplasmosis),

Drugs (e.g. NSAIDs, Vaccines), Sarcoidosis, SLE, CNS Vasculitis, VKH

2. Protein- elevated levels are sensitive for pathology, but not specific

(infection, inflammatory conditions, hemorrhage, MStumors (even spinal), malignancy). Normal range 15-60 mg/dL

3. Glucose - decreased in bacterial meningitis. Normal range = 50-80 mg/dL (2/3 BS)

4. Microbiology - Stains and Cultures - bacterial, acid fast, fungal, parasites

5. Cytology – looking for malignant cells

6. Serology – e.g. CSF VDRL

23 yo male referred for bilateral disc swellingNo headachesVA: 20/25 OU, some non-specific VF loss in both eyes

Congenitally Anomalous Discs - Drusen

No real edema

Differentiating between Congenital and Acquired Disc Elevation

Feature Congenital Acquired

Nerve Fiber Layer Clear Opacified

Large Disc Vessels Anomalous Normal

Small Disc Vessels Normal Telangietatic

NFL Hemorrhage Rare Frequent

Physiologic Cup Small or absent Normal

Drusen Sometimes present Absent

Malignant HypertensionHigh Blood Pressure with Papilledema

46 yo overweight woman with loss of vision in both eyes over last 3 weeks and headaches.

Check Vital Signs

VA: 20/20 both eyes

VF: normal confrontational VFs

External, Motility, Pupil Exam Normal

Slit Lamp, IOP normal

Fundus Exam: Bilateral Disc edema – retina hemorrhage noted OD

Tentative Diagnosis:

Get Further History - negative

First Test:

Papilledema, suspect high ICP

BP very elevated 210/120

AION

65 yo man with sudden painless of vision on wakening one morning.

VA: 20/20, 20/200

VF

+ Left RAPD

External, Motility, Pupils and Slit Lamp exam normal

Fundus: C/D 0.2 OD

Severe Disc edema OS

Tentative Diagnosis: medscape.com/.../584/197/ijir584197.fig1.

What do you do next?

Giant Cell Arteritis (GCA)

Further History -what are you concerned about?

ESR <20 normal

NAION

20/80

Testing?So no neuroimaging needed

Probably no steroids

78 yo woman, with sudden loss of vision in left eye, some headache and tenderness over scalp and temple.

VA: 20/20 OD , LP OSVF: FTCF OD, Non-specific Loss OSExternal, Motility and Slit Lamp all normal

Pupils: Strong Left RAPDFundus – OD C/D 0.2

OS - disc edema with early pallor already

Diagnosis:

Management?

AION – concern for ? GCA / TA

Giant Cell Arteritis Temporal Arteritis

ESR, CRP, CBC, FBS

Admit to Hospital for High Dose Steroids

Consider Temporal Artery Biopsy

http://kellogg.umich.edu/

28 yo woman, sudden loss of vision in left eye, some discomfort over eye and with movement.

VA: 20/20 OD , HM OSVF: FTCF OD, Non-specific Loss OSExternal, Motility and Slit Lamp all normal

Pupils: Strong Left RAPDFundus – C/D 0.2 OD, 0.3 OS – no edema

Diagnosis:

Management? Classic Left Retrobulbar Optic Neuritis

MRI of Brain

Should you give steroids??

White matter lesions noted in optic

nerve and or brain

Depends on patient - ONTT

Timely Consultation and

admission with Neurology

ONTTOptic Neuritis Treatment Trial

• Some Major Conclusions

1. Treatments with Corticosteroids

a) may speed recovery of vision, BUT does not affect ultimate visual outcome in Classic Optic Neuritis

b) may delay the onset of MS (by one year) in some patients

2. Development of Multiple Sclerosis

Overall Risk - all patients with Classic Optic Neuritis

38% at 10 Years

MRI very helpful in predicting development of MS

3. Visual Outcome for most patients at 15 years follow-up was good

ONTT10 Year Follow-Up MRI=Baseline MRI

• 38% overall development of MS

• If no lesions on MRI then only 22%

• If one or more Lesions on MRI* then 56%

15 year data – No lesion 25%, 1-2: 65%, 3 or more – 78%

Recommendation – if has any lesion on MRI refer for Neurology evaluation

Archives of Ophthalmology 2003; 121: 944

20 yo woman with sudden loss of vision and pain in right eye over 3 weeks, and is having some pain. Also with some paresthesias in arms and legs

VA: LP, 20/40Pupils: 2+ Right RAPDRemainder of Eye Exam normal

– minimal disc changes

Dx: Optic Neuritis ODMRI of brain was read as negativeAdmitted to Hospital for IV Corticosteroids

2 months later– mild recovery of vision VA :HM and 20/20

Consultation with Neurology

Diagnosis:

Poor Recovery

Atypical Optic Neuritis

NMO = Neuromyelitis Optica

Neuromyelitis Optica (NMO)

Optic Neuritis +

Myelitis of the Spinal Cord

Associated with specific

NMO IgG autoantibody to water channel Aquaporin -4 (AQP4) in cell membranes of astrocytes

Can respond to IV Methylprednisolone , but if not

Consider:

Plasmapharesis / Exchange

Rituximab

Visual Loss and Weakness, Numbness (Often below a definite level of spinal cord), Loss of Bowel or Bladder Function

NMO Not the same as MS . They differ - immunologically (cellular vs. Ab)- radiologically- in treatment response

Suspect NMO in

pt with optic

neuritis with

poorer visual

recovery

68 yo man with sudden loss of vision OD noted after heart surgeryNo headache

VA: NLP, 20/40Pupils: 4+ Right RAPDRemainder of Eye Exam normal

DDx: Retrobulbar Optic Neuritisvs. Compression / Ischemia / ?

MRI of brain was negative

Diagnosis?

Further Management?

PION = posterior ischemic optic neuropathy

Further History of GCAESR, CRP, CBC

46 yo woman with loss of vision in right eye over 3 weeks, and is having some pain.

VA: 20/100 20/20EOM: Full Pupils: 2+ Right RAPDSLE,IOP, Fundus – normal – no disc changes

ESR = 6 (normal)

Dx: Optic Neuritis ODMRI of brain was read as negativeOpted not to treat but observe

F/U 2 weeks later – no improvement in symptoms and now VA : 20/400 and 20/40

WHAT NOWWhat do you notice about her?

Further Testing?

Compressive Optic Neuropathy

Graves Ophthalmopathy

Think about Orbital Disease

CT!

25 yo woman complains of headaches and occasional episodes of transient bilateral visual loss

• Exam: 20/25 OD and 20/20 OS

Confrontational VFs were normalPupils – PERRL –no RAPD. Eye exam otherwise normal except for bilateral disc

elevation with NFL opacification and few splinter hemorrhages.

What do you suspect and what do you do next?

PapilledemaFurther History/Exam – no: medications or toxins, trauma, or sleep apnea

- normal BP, overweight

MRI of brain – negative

LP: Opening pressure =340 mm, CSF- no WBC, RBC, normal – protein + glucose

Working Diagnosis?

Pseudotumor Cerebri

(IIH= Idiopathic Intracranial Hypertension)

(not Benign)

Idiopathic Intracranial HypertensionAKA: Pseudotumor Cerebri, Benign (not) Intracranial Hypertension)

Incidence:

1/100,000 overall, 2/100,000 women, 8-20/100,000 overweight women

Diagnosis:Elevated ICP opening pressure (>200-250 mm H2O)

You must rule out other causes before making firm diagnosis

(Negative History, Negative MRI (sometimes MRV too), Negative CSF analysis)

Treatment:

DEPENDS ON STATUS OF SYMPTOMS AND VISION

- If headaches are medically controlled and there is no significant visual loss:

Observation (VF monitoring) and Weight Loss maybe all that is needed

- If there is significant headache or visual loss, then treatment needs to be more aggressive:

Close VF monitoring, PO Acetazolamide, Serial LPs, IV Acetazolamide or Steroids

Surgical – Lumbar Drain, ON Sheath Decompression or Neurosurgical Shunting procedures

35 yo woman with chronic visual loss over months and some headaches

• Exam: 20/70 OD and 20/50 OS

Confrontational VFs were not normalIOP: 13,14 mmHgPupils – PERRL –no clear RAPD Eye exam otherwise normal

except for bilateral disc changes noted.

What do you suspect and what do you do next?DDX: Glaucoma, Optic Atrophy (causes: compression, toxic, etc.)

Further History/Exam – no: family history of vision loss or glaucomaColor Vision – 4/7 OD, 3/7 OS

VF testing - Optic Atrophy

Compressive Lesion

Low Tension Glaucoma versus Other causes of Optic Atrophy

Low (Normal) Tension Glaucoma (LTG, NTG) :

Glaucomatous Cupping with corresponding VF loss,

but repeatedly normal IOP

Q: When is apparent NTG not NTG?

or When do patients with NTG need further work-up?

NTG is fairly common, but your suspicion for something else should be elevated when:

- younger person with optic atrophy or cupping

- color vision loss (glaucoma does not have color vision loss early on)

- Pallor of disc rim (pallor not usually seen in early glaucoma)

- VF loss out of proportion to the cupping present

42 yo man with poor vision and optic atrophy discovered on exam

• Exam:

20/70 OD and 20/200 OS

Confrontational VFs showed some constriction

IOP: 13,14 mmHg

Pupils – PERRL – with mild left RAPD

Remainder of Eye exam otherwise normal

except for bilateral disc changes noted.

What do you suspect and what do you do next? Bilateral Optic Atrophy –etiology unknown

Bilateral Disc Pallor

Further History including FHxVisual Field testingNeuroimaging?

Optic Atrophy / Disc PallorSeen with Damage to the Retina (NFL / Ganglion Cells),

Optic nerve, Optic Chiasm or Optic Tract

Causes:

Ischemia - e.g. past AION or PION

Compression - e.g. Pituitary Tumor, Carotid artery, Hydrocephalus, Graves Ophthalmopathy

Chronic Papilledema - compression +/- ischemia – see high ICP list

High IOP - e.g. Glaucoma, Ischemic

Inflammation - e.g. past Optic Neuritis, MS, Meningitis, Sarcoidosis, Autoimmune, Vasculitis, Infectious

Trauma – direct or indirect traumatic optic neuropathy

Toxic / Nutritional Deficit – e.g. Medications: Ethambutol, etc.

Methanol, Ethylene Glycol, Heavy Metals (Pb, Hg, As),CO, CCl4Vitamin Deficiencies (B1,B12, Folate, niacin)

Congenital / Hereditary – e.g. Isolated : Autosomal Dominant Optic Atrophy (ADOA), Leber’s (LHON)**

Non–isolated: Metabolic***, neurodegenerative diseases, Behr’s SyndromeFriedreich’s and Spino- Cerebellar AtaxiasAssociated Hearing Loss: Wolfram’s Syndrome (DIDMOAD), Some ADOA

Retinal Damage - (False Ocular Localizing Sign) - CRAO, CRVO, Ischemic PDR, S/P PRP, Retinitis

Temporal

Pallor

(Loss of ganglion cell axons)

The Diagnostic Yield of the Evaluation ofIsolated Unexplained Optic Atrophy

form Univ. of Cincinnati and Univ. of Iowa (K. Golnik, A. Lee, R. Kardon, et. al. )Ophthalmology 2005; 112: 757

1110 Charts reviewed - Exclusion Criteria included: children (<18 yo), other neurologic deficit (non-isolated), know

ocular or systemic disorder for optic neuropathy, history suggestive of etiology: e.g. prior intracranial tumor, syphilis, GCA, toxin exposure, nutritional deficiency, family history

Leaving : 91 cases of unexplained Isolated Optic Atrophy

All underwent some form of neuro-imaging and Lab Testing* done in 51 of 91 cases

Important Results

18 patients (20%) had a compressive lesion** – e.g. Meningioma, Pituitary adenoma, Craniopharyngioma

None of the patients had abnormal Lab testing* that could be linked to the Optic Atrophy

Conclusions

Many etiologies for optic atrophy can be determined by careful history, review of any records and past imaging studies, and acomplete eye exam and visual fields. In cases that are truly “unexplained” and isolated a neuroimaging study is appropriate since 1 in 5 patients were found to have a significant compressive lesion. Screening lab studies are not warranted, but should be ordered based on clinical presentation.

Disc Scenario Visual Loss More Likely Diagnoses

1. Bilateral Elevation/Edema Little or none Early Papilledema / High ICPPseudo-papilledema (Anomalous discs)

2. Bilateral Edema Significant Simultaneous or Closely Sequential AION or Optic NeuritisSome Compressive and Toxic Optic Neuropathies, MeningitisLate - Severe Papilledema

3. Unilateral Disc Edema Little or none Papillophlebitis, Mild Diabetic Papillopathy

4. Unilateral Disc Edema Significant AION, Papillitis (Anterior Optic Neuritis)Compressive, Ocular (Hypotony, Uveitis, CRVO)

5. Bilateral Disc Pallor Bilateral Significant Past Severe Bilateral ON (AION, Optic Neuritis, Papilledema)Past or present CompressionCongenital or Hereditary CNS/Metabolic ProblemPast Severe: Glaucoma, CRAO, CRVO

6. Unilateral Disc Pallor Unilateral Significant Past Severe AION, Optic Neuritis or CompressionPast Severe: Glaucoma, CRAO, CRVO

7. No Disc Changes Significant Unilateral Retrobulbar Optic Neuritis, PION, Early Compression, Traumatic ON

8. No Disc Changes Significant Bilateral Bilateral PION (Hypotensive or GCA)Early Chiasmal Process, Early Toxic Optic Neuropathy

9. Increased Cupping Significant VF Loss Glaucoma, Normal Tension Glaucoma or Mimic

Some clear Indications for Neuroimaging (CT, MRI brain or orbits)

*Remember Imaging is not Necessary for every patient with diplopia, ophthalmoplegia,

strabismus, nystagmus, visual loss (VA or VF), ptosis, disc edema / pallor, or headache.

Yet Consider for imaging for:

1. Cranial Nerve Palsies – non-isolated any age, or isolated in younger patients (<50 yo),…

2. Ophthalmoplegia – unilateral associated with orbital signs

3. New Visual Field loss that respects the vertical midline

4. Bilateral Disc Edema – when associated with headache or visual loss

5. Optic Neuritis – history of eye pain (movement) , sudden loss of vision, +RAPD , +/- disc edema

6. Bilateral or Unilateral Disc Pallor – not previously explained

7. Nystagmus – not explained by drugs, toxins, pre-existing infantile nystagmus, metabolic derangements

8. Ptosis – when associated with other neurologic or orbital signs or symptoms

Approach to Suspected Optic Neuropathy

1. Remember 3 most common conditions

1) Papilledema, 2) NAION, and 3) Classic Optic Neuritis

2. If patient does not fit one of these conditions well:Consider DDX for optic neuropathies and ask further history and do more detailed exam as needed.

Ocular Findings that can direct work-up: Signs of Uveitis, Bilateral Temporal Disc Pallor, etc.

VF testing very useful – e.g. specific patterns help direct diagnosis: hemianopic, centrocecal, etc.

3. Testinga) First Consider: Blood Pressure, ESR, Glucose Level

b) Neuroimaging – especially for

- Typical or Atypical Optic Neuritis

- Papilledema not explained by history/ exam (e.g. medications, BP)

- Isolated Unexplained Optic Atrophy

c) Other Testing

1) Acute Optic Neuropathy:

- LP: especially if suspect high ICP or CNS inflammatory condition

- Other Testing: CBC, ANA, ACE, FTAbS, B12, etc. - as clinically indicated

2) Optic Atrophy

- Screening Lab Testing not of much benefit in Unexplained Optic Atrophy

- Lab Tests as indicated by History and Findings

Approach to Suspected Optic Neuropathy

Treatment Options:

Treat the Underlying Condition if possible

Consider Use of Corticosteroids – if no clear diagnosis with other treatments

dependent on working diagnosis and risk factors (e.g. TB, DM, etc)

Other Options: Plasma Exchange – used in NMO Optic Neuritis (Archives 2012; 130:858)

Rituximab is a monoclonal antibody (CD20, from mouse tissue) that binds to a

receptor on the surface of B cells. These cells are then destroyed and their levels in the circulation are decreased. It is approved for use in the treatment of lymphomas, leukemia, and autoimmune disorders.

Steroids and Optic Neuropathies

Responsive Unknown or Not Proven

• AAION (GCA)*

• Demyelinating Optic Neuritis**

• Some Atypical Optic Neuritis

e.g. Sarcoidosis

Wegener’s

Autoimmune Optic neuropathy

Orbital Pseudotumor

• Compression Optic Neuropathy from

Graves Disease

• NAION***

• Toxic Optic Neuropathy

• Traumatic Optic Neuropathy

• Congenital / Familial (e.g. LHON)

• Compressive Optic Neuropathy**** (except Graves)

• Papilledema – though sometimes steroids can temporarily lower ICP and thus indirectly help optic neuropathy

Beware of Conditions that steroids can

exacerbate: e.g. DIABETES, Osteoporosis,TB, Syphilis, Herpetic, Fungal

Typical Tapering Steroid Treatment

• Maybe first: IV – Methylprednisolone (Solumedrol)

250 mg 4x/d or 1 gram once a day for 3 days

• Then Oral Prednisone Taper for at least 2 weeks:

• 1 mg/kg

• Example: 60 kg man

• 60 mg for 4 days then 40 mg for 4 days then 20 mg for 4 days and then 10 mg until patient follows up and then can decide whether to stop medication or continue at lower dose

Summary

• First Consider one of most common causes

(Does it fit the presentation/ Natural History?)

and then manage appropriately

If the presentation or natural course do not fit one of the most common optic neuropathies, then consider further testing or referral

1. Classic Optic Neuritis2. NAION3. Papilledema

(High ICP)

Thank You

Behold, children are a heritage and gift from the LORD

PSALM 127:3

The Freedman Family

The LORD is my light

and my salvation;

whom shall I fear?

Psalm 27:1

Appendix

Acute Optic Neuropathy(As evidenced by unexplained VA loss, VF loss, RAPD, Disc Changes)

“Classic” Demyelinating Optic Neuritis: Related to MS or NMO*, Idiopathic, ADEM**

Other Optic Neuritis (Often not classic course / “Atypical”) Post Viral or ImmunizationAutoimmune (40-60 yo, responsive to steroids)Contiguous Inflammation (Meninges, Orbit, Sinuses- e.g. Sphenoid Sinus)CNS VasculitisInfectious: HSV, VZV, Toxoplasmosis, HIV, Bartonella, Cryptococcus, Hepatitis, Syphilis, TBOther: Sarcoidosis, Optic Perineuritis (IOIS), IgG4-ROD, GBS (rare)

IschemicNon-Arteritic Anterior Ischemic Optic Neuropathy - NAIONArteritic Anterior Ischemic Optic Neuropathy – AAION (GCA)Posterior Ischemic Optic Neuropathy - PION (peri-operative, arteritic, non-arteritic)Post-op CE or PPV

Compressivee.g. Pituitary Apoplexy, Thyroid Orbitopathy, Carotid Artery, Tumor …

Hereditary: LHON

Acute High ICP

Traumatic: Head (Forehead, Temple), Orbit, Globe

Paraneoplastic: Associated often with Small Cell Lung CA and CRMP-5 protein

Medications / Toxins: e.g. Ethambutol, Chemotherapy, Methanol, Ethylene Glycol

Radiation Optic Neuritis: can see months to years after treatment

With or Without Disc Swelling

Timing

Abrupt – ION, LHON

Subacute – optic neuritis

Insidious – compressive or

metabolic

Character

Dark spot – optic

neuropathy

Metamorphopsia -

maculopathy

Unexplained Bilateral or Quickly Sequential Acute Visual LossRapid loss of vision in both eyes simultaneously or sequentially with minimal ocular findingsVascular

Hypotension – e.g. PION after trauma, surgery, code

Severe Systemic Hypertension

Vertebrobasilar Insufficiency

Temporal Arteritis – e.g. PION

RetinalParaneoplastic: MARS and CARS*

Optic Nerve

LHON

Bilateral / Sequential Retrobulbar Optic Neuritis (e.g. Neuromyelitis Optica -NMO , MS not as likely)

Other Inflammatory – Post-infectious, Autoimmune, Infectious ON, Meningitis, Vasculitis, Sarcoidosis, GBS

Other Optic Neuropathy – Toxic (e.g. Methanol, Chemo), Nutritional, infiltrative

Paraneoplastic Optic Neuropathy* (e.g. small cell Lung CA)

PION – e.g. post-op, trauma, shock

CNS

Migraine

Compressive Lesion – e.g. rapidly expanding like pituitary apoplexy

Cortical Blindness – hypoxia, hypotension, PRES*,see more complete list under unexplained visual loss

Other

Sudden Refractive Changes: e.g. loss of accommodation, high Blood Glucose, etc.